This invention relates to methods for increasing the incidence of females in the offspring of mammals, especially humans.
In mammals, the sex is determined by two different types of sperm, which have either an X-chromosome (X-sperm) or Y-chromosome (Y-sperm). Fertilization with Y-sperm produces males. The assumption that these two kinds of sperm differ in size and weight has led to a series of investigations, in which the separation of the X- and Y-sperm has been attempted by sedimentation, centrifuging, electrophoresis, variation in pH-value or flotation. See, e.g., U. S. Pat. No. 3,687,806; Schilling, Erich, J. Reprod. Fert. (1966) 11, 469-472; Chem. Abstr. 66, 44818q (1967); A. M. Roberts, Nature, Vol. 238, pp. 223-225 (1972) ; Lang, J. L., Chemtech, March, 1973, pp. 190-192; Symposium, "Sex Ratio at Birth--Prospects for Control," American Soc. of Animal Sci., July 31-Aug. 1, 1970; Beatty, R. A., Bibliography (With Review) Reproduction Research Information Service, Ltd., Biblphy. Reprod. 23:1, Jan. 1974.
In U.S. Pat. No. 4,009,260, I claim methods for increasing the incidence of males in the offspring of mammals by artificially inseminating a fertile female with a Y-sperm enriched sperm fraction of that mammal obtained by maintaining at least the sperm portion of progressively motile sperm-containing semen, either as such or suspended in an aqueous suspending vehicle physiologically acceptable to the sperm, as an upper layer in vertical interfacial contact, at a temperature at which the motile sperm are motile, with a lower discrete layer of a first aqueous contacting medium physiologicaly acceptable to the sperm and in which the motile sperm migrate downwardly at a slower rate than in the upper layer, until a portion only of the motile sperm of the semen having migrated downwardly into the contacting medium, thereby producing a contacting medium containing a higher proportion of Y to X sperm than in the starting sperm, and repeating the step at least once, employing in the upper layer the motile sperm which have migrated to the first aqueous contacting medium and as the lower layer of second aqueous contacting medium physiologically acceptable to the sperm and in which the motile sperm migrate downwardly at a slower rate than in the first contacting medium.
In U.S. Pat. No. 4,007,087, I claim a method for enhancing the survival rate of sperm subjected to frozen storage by subjecting sperm to the above-described process prior to freezing.
The process of U.S. Pat. No. 4,009,260 relies upon enrichment of the Y-sperm in the motile sperm-fractionation process to increase the incidence of conception of male offspring. Unfortunately, the process cannot be used to produce an X-sperm-enriched sperm fraction.
The importance of a method of increasing the incidence of female offspring is obvious. In milk cows, female calves are always preferred, except when a breeding bull is desired. In racing horses, mares are often preferred over stallions. Many humans desire or would prefer girls as progeny.
E. Adashi et al., reporting in Fertility & Sterility, 31, No. 6, 620-626 (1979) noted a sex ratio (female/male) of 1.3-1.4 in the offspring of women in whom ovulation was induced with clomiphene ("Clomid," Merrell-Dow). However, L. Klay, Fertility & Sterility, Vol. 27, No. 4, April 1976, reported 11 males and 6 female births in women on clomiphene-regulated ovulation. William H. James, British Medical Journal, Vol. 281, p. 711, 1980 reported that female offspring is more likely to be born than male following both clomiphene and gonadotrophin administration. However, the percentage of female offspring (56-57%) is not high enough to render such therapy a predictable method of producing female offspring.
I have found that, surprisingly, in accordance with this invention that the incidence of female offspring which are conceived by women in whom ovulation has been artificially induced can be markedly increased, even in women artificially inseminated with a Y-sperm enriched sperm fraction.